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The present invention refers to an analytical device according to the introduction of claim 1 and a process for the analytical optical detection of liquid samples.
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For the optical determination of fluid chemistry or liquid samples respectively photometric analysis is commonly used and known in the art. E.g. proposed is a disc like rotatable device on which a plurality of receptables like cuvettes are arranged for the collection of fluid samples, the receptables each are arranged within a photometric detection path, the respective light beam being absorbed partially for the analysis of the sample or its chemistry respectively photometric determination of fluid chemistry is in particular used for blood analysis, urea analysis or for any other liquid samples, where various fluid samples such as e.g. blood samples are being placed within sample cuvettes and light beams are being passed through the cuvettes, the light being partially absorbed for analysis of the blood samples.
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In the
US 5 122 284 a rotatable device is described, where optical analysis of a biological fluid, arranged in a cuvette, is proposed. A light beam, perpendicular Oriented on to the disc surface is deflected in direction to the cuvette parallel to the plane of the disc through the cuvette and then detected for analytical purpose.
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In the
US 5 478 750 again photometric analysis of blood samples arranged on a rotatable disc is described, measuring the concentrations of substances like blood cell components within the liquid blood sample. The various fluid samples are arranged in cuvettes on the disc and for analytical purpose a light beam guided in perpenticular direction onto the disc surface is deflected in direction to the cuvettes within the plane of the disc.
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In all known analytical devices the arrangements of the optical means and of the liquid sample containing cuvettes are arranged such, that the direction of the light beam is in line with the radius of the rotatable disc, which means the optical deflection means or the reflective mirrors are arranged perpendicular to the radius of the rotatable disc.
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To minimize any absorption or negative influence of the material of the rotatable disc it is usually made out of a thermoplastic transparent polymer, such as e.g. PMMA, Polycarbonate, Polystyrene, transparent copolyamide, etc. where so far PNIMA has preferably been used. The disc like analytical devices are usually manufactured using injection moulding technique. The optical means for the deflection of the light beam into the direction to the liquid sample containing cuvettes is achieved by providing a surface within the disc in an angle of 45° to the plane of the disc, so that the perpendicular arriving light beam is deflected without practically no absorption by the transparent polymer of the disc like device. For producing such surfaces with a 45° angle usually respective inserts are arranged within the mould which means, that for each reflection surface a respective insert has to be arranged within the mould before the injection moulding procedure. The liquid polymer-melt is introduced into the mould at the centre of the disc, which means at the rotation axis of the disc like device, the flow of the liquid polymer is directed radially outward which may cause problems at the locations, where the inserts are arranged for the production of the reflective zone. The problem occurs due to the fact that the liquid polymer-melt is flowing around the insert, which is arranged perpendicular to the radial outward direction of the flow, so that the flow surrounds on both sides the insert for being mixed again at the backside of the insert. Practical experience showed, that due to this mixing zone on the reflective surface at least partial polarisation of the light to be deflected in the direction to the cuvettes may occur, which of course is not desirable.
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Furthermore the insertion of all the various inserts before the injection moulding procedure is time consuming and as a consequence the production procedure as used so far for the production of the known disc like devices for analytical purpose is not optimal.
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It is therefore one object of the present invention to optimize the production process for analytical devices as described above for photometric detection, where the surfaces of at least most of the reflective surfaces or mirror like surfaces may guarantee optimal reflective properties, so that the deflection of the light beam is not effected by any defects within the surface.
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It is a further object of the present invention to reduce the handling before and/or during the production of photometric analytical devices as described above in respect to simplify the placement of any inserts into the moulding tool establishing the mirror like or reflective surfaces within the disc like device for photometric analytical purpose.
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As a consequence according the present invention proposed is an analytical device according the wording of claim 1 and a process for the production of an analytical device according the wording of claim.
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Proposed is a device comprising a rotatable disc on which a plurality of cuvettes is arranged for collecting liquid samples to be analyzed. Furthermore reflection means are arranged within the disc like device to direct a light beam through the cuvettes, the reflective means are arranged such, that at least part of the light beam is deflected or guided in a direction in an angle to the respective radially outward direction on the disc which means the respective radius from the disc rotation centre or axis through the respective reflection means.
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According to one aspect of the present invention at least part of the optical means, primarily the means being responsible for the deflection of the arriving light beam into and through the receptable for the liquid sample is arranged in an angle to the respective radially outward direction which is different from 90°. With other words the surface, or at least part of it, of the optical means is arranged in an angle different to 90° to the respective radius connecting the optical means with the rotation axis of the disc. As a consequence the light beam also is guided through the receptable such as the cuvette, containing the respective liquid sample to be analyzed in a direction, which is in an angle to the radially outward direction on the disc. A further consequence is, that the entrance plane through which the light beam is entering into the receptable or cuvette, also called detection window, is also arranged in an angle to the radially outward direction on the disc, which is different from 90°. Or defined with other words the plane of the detection window does have an angle to the radially outward directed rotation force, which is different from 90°. Finally the additional optical means to guide e.g. the light beam after detection out of the disc plane can again be arranged such that its surface is in an angle different from 90° to the radially outward direction on the rotatable disc.
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According to one possible embodiment, according the present invention there are arranged a plurality of receptables provided or cuvettes respectively for the collection of liquid samples such as e.g. blood, urea and the like and/or additional additives and reagents to be optically analyzed. At each receptable at least one preceding reflective surface is arranged within the disc which is a mirror like surface arranged in an angle of 45° to the plane of the disc for the deflection of a perpendicular arriving light beam into the plane of the disc and guiding it through the receptable or cuvette containing the liquid sample such as e.g. blood. Of course all the mirror surfaces should be arranged such, that all the light beams arriving from the same side of the disc are guided through the respective liquid sample receptable such as the cuvette. Furthermore all the plane mirror like surfaces, or at least part of it, are arranged in an angle to the radially outward direction on the disc which is different from 90°, so that the deflected light beam is in an angle to the radially outward direction.
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In direction of the light beam after the various receptables or cuvettes respectively again reflective surfaces or deflection mirrors can be arranged within the disc like body such that the light beam after detection arriving from the receptables or cuvettes respectively is deflected preferably in a perpendicular direction out of the plane of the disc like device. Therefore this reflective surface or mirror again is in an angle of 45° to the plane of the disc, where again preferably all mirrors are arranged such that the respective light beams are guided into the same direction out of the disc plane. It can be either the same direction from which the initial light beam is guided on to the disc plane or the opposite direction out of the disc like device.
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The great advantage of arranging the optical means as proposed above is, that during the injection moulding procedure the liquid polymer-melt is not symmetrically surrounding the mirror surface or deflection plane and therefore in the middle of the surface no irregularities may occur due to the mixing of the polymer-melt. This mixing zone could either be displaced to a side area of the reflective surface where the light beam is not hitting the surface or even in case, that the surface is arranged parallel to or within a radially outward radius, the mixing zone is completely out of the surface. A further advantage of the arrangement as described above is, that at the entrance window for the light beam or the detection window resp. of the receptable no gas bubbles will accumulate within the liquid to be detected. This due to the fact, that the plane is not arranged in an angle of 90° to the radially outward rotation force direction and as a consequence the gas bubbles move along the window towards an edge of the entrance plane. At the respective edge, a removal of the gas bubbles can be achieved by the arrangement of so called microchannels. As a consequence the light beam is not being affected by the undesired gas bubbles.
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According to another aspect of the present invention it is proposed to arrange a circular mirror or reflection surface, which is arranged on a segment of a circle on the disc like body of the analytical device. The cross section of the reflective surface is linear and is preferably arranged with an angle of approximately 45° to the plan of the disc. As a consequence the surface of such an optical means is not plain but rounded, which as a consequence is widening within the disc plane an arriving light beam before entering into the receptable or cuvette. With other words only the very central portion of the arriving light beam, which again preferably arrives perpendicular to the plane of the disc is deflected within a radially outward direction of the disc, and the remaining part of the light beam is widened and as a consequence most of the light beam is in a direction in an angle to the radially outward direction of the disc. Furthermore after the cuvette, again a respective collecting optical means can be arranged, which again preferably is circular, arranged within a segment of a circle of the rotatable disc. In addition this mirror or reflective surface is designed such, that the widened light beam is collected and focused e.g. onto a phototetecting means which means the widening of the first reflective surface is revoked or cancelled to a narrow light beam. But as narrowing a widened light beam to a narrow light beam is well known in the art at this place no further details should be described in respect to any further optical arrangements.
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According to a further similar embodiment not only segments of the circle are covered by various circular mirror like surfaces or reflection surfaces, but the reflection surface is covering a total circle on the optical analytical disc like device.
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The great advantage of circular optical means is, that only a very limited amount of inserts has to be placed within the mould before or during the injection moulding process for the production of the disc like device. Of course in this case again there may occur the problem of undesired mixing zones of the liquid polymer on the side of the reflective surface, but due to the fact that the arriving light beam before entering into the receptable is widened the problem due to uneven zones on the reflection surface is of minor importance. Furthermore, as the first optical means for deflecting the arriving light beam into direction to the receptable are arranged near to the central axis of the disc it might be possible to provide entrance holes for the injection of the polymer-melt near to the place, where the reflection surfaces are arranged.
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Further embodiments and characteristics of the present invention should be explained in more details with reference to the attached figures, in which examples are shown in more details.
- Fig.1
- shows schematically in plan view an analytical device according to the present invention showing two sections provided for photometric analysis,
- Fig.2
- shows a cross section along line I-I from fig.1,
- Fig.3
- shows a further possible design of the device of fig.1 along the line I-I,
- Fig.4
- shows a possible design of the receptable or cuvette, suitable for photometric analytical detection within a section as shown in fig.1,
- Fig.5
- shows a further possible arrangement in plan view for the optical detection, suitable for a disc as shown in fig.1,
- Fig. 6a&6b
- demonstrate an advantage of the arrangement as described in the present invention,
- Fig.7
- shows an alternative arrangement of an optical, analytical section, suitable for arrangements on a disc according the present invention, and
- Fig.8
- shows the progression of a light beam within an optical, analytical arrangement as shown in fig.6.
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Fig.1 shows in plan view an analytical device according the present invention, comprising primarily a disc like body 1 being rotatable around a central axis 3. In direction to the periphery 8 of the disc like device, a plurality of sections are arranged with arrangements 5 suitable for the optical or photometric analytical detection of a liquid sample. For that purpose a plurality of receptables or cuvettes 7 are arranged on or within the disc like body 1. Preceding to the receptable or cuvette 7 arranged is a first optical means 9, in form of a plane reflective or deflective surface for the deflection of an arriving light beam into direction of the cuvette 7. After the receptable or cuvette 7 again a second optical means 11 is arranged which again is a deflective or reflective mirror surface.
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To better understand the particular arrangement for optical analysis, fig.2 shows a sectional few along line I-I from fig.1.
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Fig.2 shows one optical analytical arrangement 5 out of fig.1 in the sense of a cross sectional view through the disc like body 1 of fig.1. The first optical means 9 is a deflection mirror like surface 10, which is arranged in an angle of 45 ° to the plane of the disc like body. As a result an arriving light beam 21 is deflected in direction to the cuvette 7, in which a liquid sample such as e.g. a blood sample is arranged. The light beam is entering into the cuvette 7 through an entrance plane or detection window 14 and is leaving the cuvette 7 through a second plane or window 16. After detecting the liquid, which means after being partially absorbed, the light beam is guided onto a second optical means 11 which again is represented by a deflective mirror like surface 12 which again is arranged in an angle of 45 ° to the plane of the disc like body 1.
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The second optical means 11 is not absolutely necessary, as according one possible embodiment the light beam 21 after having passed the cuvette 7 can penetrate in plane of the rotatable disc like body 1 out of the outer periphery border 8 for being detected e.g. by a photometric detection element.
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The cuvette 7 preferably is an "open" cuvette for easy filling reason and may be covered by a film- or plate-like cover 23 which may be removably arranged on the disc like body 1 after filling the various cuvettes or receptables 7. In general the cover is arranged firmly and filling of the cuvette can be achieved through microchannels, which in general are arranged within disc like analytical devices. The arrangement of such micro channels is well known from the art and therefore no further explanation has to be given at this point.
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In fig. 3 a further possible optical analytical arrangement 5 is shown along the line I-I of fig.1. In principal the optical arrangement is equivalent to the one shown in fig.2 with the exception, that the second optical means 11 is having a deflective mirror like surface 31 guiding the light beam 21 into a direction out of the plane of the disc like body 1, which is opposite to the direction from which initially the light beam 21 arrives into the arrangement.
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As already described above, the difference of the optical arrangement compared to the state of the art is, that the optical means for deflecting the light beam is arranged such, that the light beam direction through the receptable or cuvette with the liquid sample to be detected is in an angle α to the radially outward direction, which means, the light beam is not equivalent with a radial outward direction of the disc like body. The advantage is, that during production of the disc like body by using injected moulding technique the liquid polymer-melt injection in the centre of the disc is not surrounding the first optical means in a symmetrical way, so that the mixing zone of the polymer-melt is not in the area, where the light beam is being deflected. As a consequence no undesired effects such as e.g. polarisation of the light may occur on the reflective surface.
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In case of a closed and/ or completely filled receptable or cuvette 7 the design as shown in fig.1 to fig.3 may be applied. But in case of a only partially to be filled cuvette and a cuvette filled with additional amounts of liquid, a different design could be chosen, as shown e.g. in fig. 4.
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Usually for an analytical purpose different liquid chemistry samples are used such as e.g. blood samples, where in a first item only the sample as such is analytically detected. In successive further items additional additive and reactants are added into the cuvette or receptable 7. As a consequence it is important, that already in the first step or first item the light beam is guided through a "completely filled" cuvette, which means that there are no empty holes on the path of the light beam through the cuvette. Therefore according to fig.4 it might be necessary to use a different design of a cuvette 7 to get reliable analytical results with an arrangement as proposed according to the present invention. It is e.g. possible instead of using a rectangular cuvette7 a cuvette design as shown in fig.4. The cuvette 41 as shown schematically in fig.4 does have an additional volume in direction to the centre of the rotatable disc. In the first item a first sample covering Vl is given into the receptable or cuvette 41, the volume is such, that the light beam 21 is completely travelling through the liquid sample. After the addition of a second volume V2 e.g. through a microchannel (not shown)and appropriate mixing of the total volume again a further analysis is executed, again the light beam 21 is travelling through a totally filled volume V1 and V2 for detection purpose. In a third step a further volume V3 is added and after a further mixing process an additional analytical step by using the light beam 21 is following.
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The design as shown in fig.4 of course only represents one possible example for the better understanding of the problem which may occur by using liquid samples with different volumes which means with different chemical steps to be analytically detected. Any other possible design can of course be used -important is, that already for the detection of the first sample volume the light beam 21 is travelling completely through the liquid sample.
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Furthermore it is of course possible to place the analytical arrangement in a perpendicular direction to the radially outward direction, as shown in fig.5.
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By using fig. 6a & 6b one great advantage of the present invention should be described in details. Fig. 6a shows an arrangement 5' as arranged on a conventional disc as known in the art. The first mirror 9, the cuvette 7 and the second mirror 11 are arranged on a line, which is in line with the radially outward direction on the rotation disc 1. With other words the light beam 21 guided through the cuvette 7 is identical with the radially outward direction 2, which also corresponds to the connection line between the first mirror 9 and the rotation axis 3 of the disc. A disadvantage of such a kind of an arrangement is, that due to the perpendicular arrangement of the entrance plane 14 or the detection mirror, through which the light beam 21 is entering into the cuvette or liquid receptable 7, gas bubbles may accumulate mainly in the centre of the window 14. Within fig. 6a such gas bubbles are designated with the referential number 20. The forming of such gas bubbles can influence the light beam and therefore a wrong analysis result may be achieved.
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Within the arrangement as shown in fig. 6b and as designed according to the present invention, the entrance plane 14 for the entrance of the light beam 21 into the liquid receptable 7 is in an angle to the radially outward direction, which is different from 90°. As a consequence the direction of the light beam 21 is not identical or in line with the radially outward rotation direction 2, but is including an angle α. As a consequence the gas bubbles will move towards the upper edge of the entrance window 14, where they can be evacuated through a microchannel 1B. As a consequence by using the arrangement 5" as shown in fig. 6b and as defined within the present invention, no forming of entrance window 14 can occur, which can influence the light beam 21.
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Fig.7 shows in plan view and schematically a further possible embodiment according to the present invention. The embodiment according to fig. 7 is showing in plane view a first mirror arrangement 51 being a circular designed reflective or deflection surface representing part of a segment of a circle arranged on the disc like body 1 of the analytical device. The mirror like or reflection surface 51 is on one side circular and in addition does have a linear cross section, so that a light beam arriving in a perpendicular direction onto the disc plane is being deflected in direction to the cuvette or receptable 7 containing the fluid sample. As a consequence also the succeeding reflection or mirror like surface 53 may be designed with a circular shape and again may have a linear cross section.
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In fig.8 schematically the progression of a light beam 61 is shown, which arrives in a perpendicular direction onto the plane of the disc like body and which is deflected by the mirror like surface 51. The light spot 55 on the first reflection surface 51 is widened within the disc plane due to the non even circular surface of the first mirror and is proceeding as widened light beam 61 through the receptable or cuvette 7, containing the liquid sample to be optical detected. Due to the linear cross section e.g. in an angle of approximately 45° to the plane of the disc no widening occurs perpendicular to the plane of the disc which means out of the disc plane. Finally the widened light beam 61 is collected by the succeeding second mirror like reflection surface 53, where the light beam is arriving as widened light spot 59. For the succeeding optical detection and analysis of the light beam a further optical arrangement can be placed, in which the widened light beam again is collected to a light beam with a reduced diameter, comparable e.g. with the entering light beam at the spot 55 on the first mirror like surface 51. But as this is common practice in the art at this place no further explanation should be given about the succeeding optical arrangement.
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As a consequence again most of the light is travelling from the spot 55 on the first mirror like surface 51 through the receptable or cuvette 7 in a direction, which is not equivalent with the radially outward direction of the disc like body 1.
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Of course in fig.7 and 8 only one analytical arrangement is shown, while in practice spread over the whole disc like body 1 a plurality of analytical arrangements may be placed. The great advantage of the arrangements according to fig.7 and 8 is, that at the production of the disc like body and for creating the respective mirror like reflective surfaces 51 and 53 only a reduced amount of inserts have to be placed within the mould for the injection moulding process. Either, a total circle can be used, on which the various protruding insert segments are arranged for creating the reflective surfaces 51 or as an alternative an insert can be used where a circular reflective surface 51 is created which represents a complete circle and not individual segments. The same of course may happen when creating the second succeeding reflective mirror like surface 53.
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To prevent any mixing zones in the area of the reflective surface the injection holes or openings for the melted polymer could be arranged just near to the insert sections, so that the mixing zones of the melt will not be in the centre of the reflective surface.
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The examples as shown in figs. 1 to 8 are of course only examples to explain the present invention in more details and do not represent any restrictions for the designs for optical analytical arrangements for the analysis of chemistry and/or liquid samples in particular in biochemical and medical analysis. Furthermore the analytical devices according the present invention and which are explained by way of examples as shown in figs. 1 to 8 can be used for a big variety of applications. The main application area of course covered chemistry and sample analysis in the field of bio chemistry, pharmaceutics and medicine. In particular an important application is the chemistry and the sampling of blood, urea and other liquid samples, where a great variety of analysis possibilities are possible. Usually not only blood or urea as such is used, but also in combination with a great variety of additives and reactants. Furthermore using the rotation of the disc like device e.g. blood or urea can analyzed at various steps of separation between e.g. plasma and blood cells. Of course in general any kind of sampling analysis is possible and the use of rotatable disc like devices in principal is well known in the art.
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Further more the optical analytical process as such is also known from the art which means the process using the device according to the present invention may include any kind of light beam wave lengths which are commonly used in analytical processes. For instance any kind of laser beams or commonly used light in the range e.g. from 300 to 800 nm etc. can be applied. Also the material used for the production of a disc like device is known and preferably a transparent polymer is used such as e.g. PMMA. But of course also all kind of suitable transparent polymers maybe used like e.g. polycarbonat, transparent polystyrene, transparent polyamides, etc.